Many of the cells that make up the human body are normally cells that have one nucleus within the individual cell (that is, mononuclear cells), but it is known that some types of cells have a plurality of nuclei within the individual cell (that is, multinuclear cells).
Megakaryocytes and osteoclasts are examples of multinuclear cells that are normally present in an organism (cells that exhibit their normal function while being multinuclear cells). Osteoclasts are multinuclear cells that are differentiated from hematopoietic stem cells and are cells that are responsible for the destruction of old bone tissue (bone resorption) and that participate in bone reconstruction (bone remodeling) and bone growth (Non Patent Literature 1). In addition, they also participate in the regulation of the blood calcium concentration (maintenance of homeostasis) by supplying calcium from hone to the blood through the hone resorption (Non Patent Literature 2). Megakaryocytes are multinuclear cells that are differentiated from hematopoietic stem cells and are cells responsible for platelet production.
Platelets are a blood component (cellular component in the blood) required for blood coagulation and hemostasis and are in great demand in the areas of, for example, leukemia, bone marrow transplantation, and surgery. At the present time, blood products (platelet preparations) acquired by blood donation are frequently used for platelet transfusion to patients that require the administration of platelets. However, transfusable platelets (platelet preparations) have a short retention period (effective period) post-blood collection and their supply is prone to be unstable due to blood donor shortages. As a consequence, art for the production of platelet-producing megakaryocytes from cells (for example, megakaryocyte precursor cells) derived from an organism (for example, the patient) or derived from stem cells, e.g., induced pluripotent stem cells (iPS cells), embryonic stem cells (ES cells), or hematopoietic stem cells, and art for the production of platelets from such megakaryocytes have been anticipated as art crucial for achieving a stable supply of platelets (platelet preparations) that would be independent of blood donation. As art related thereto, for example, Patent Literature 1 describes art for establishing a megakaryocyte precursor cell line that has been immortalized by the forced expressed of certain genes. Patent Literature 2 describes art in which, in order to increase the in vitro production of functional platelets (platelets that maintain their activity, e.g., hemostatic action, in vivo) from megakaryocytes, multinucleation of megakaryocytes is additionally promoted by the forced expression of certain genes.
One characteristic feature of tumor cells (cancer cells) is that cell division is more active than for normal cells and the cell proliferation rate is thus significantly higher. As a consequence, many of the anticancer agents directed to killing tumor cells or suppressing their growth use drugs that inhibit cell division in tumor cells (cancer cells). Alkylating agents, antimetabolites, and microtubule-targeting agents are examples of drugs that inhibit cell division. Alkylating agents inhibit cell division by tumor cells (cancer cells) by a mechanism of action that acts on DNA to crosslink the bases on the double strand with each other; antimetabolites, 5-FU and so forth, inhibit cell division by tumor cells (cancer cells) by a mechanism of action that inhibits DNA synthesis; and microtubule-targeting agents inhibit cell division by tumor cells (cancer cells) by a mechanism of action that inhibits mitosis by inhibiting the polymerization or depolymerization of microtubules. Numerous anticancer agents (antitumor compositions) have been developed to date, but there is still great demand for drugs that are more effective and have a low risk of side effects and for inexpensive drugs that are highly effective. For example, if it were possible to inhibit cell division by tumor cells by artificially and aggressively causing multinucleation of the tumor cells, this could be used as a novel anticancer art (anticancer agent).
Thus, a critical problem for regenerative medicine and cancer treatment is, as in the examples referenced above, to establish an art for artificially producing the multinuclear cells that carry out highly specialized responsibilities in the organism, e.g., megakaryocytes, osteoclasts, and so forth, or to establish an art that realizes the inhibition of cell division based on the multinucleation of tumor cells (cancer cells).